7YM5

Crystal structure of the Salmonella effector SseK1

Replaces:  6AGU

Summary for 7YM5

• Entry DOI: 10.2210/pdb7ym5/pdb
• Descriptor: Type III secretion system effector arginine glycosyltransferase SseK1, MANGANESE (II) ION, URIDINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: salmonella, effector, arginine glycosylation, toxin
• Biological source: Salmonella enterica
• Total number of polymer chains: 1
• Total formula weight: 35879.11

Authors

Kim, U.J.,Park, J.B.,Yoo, Y.,Cho, H.S. (deposition date: 2022-07-27, release date: 2023-08-02, Last modification date: 2024-11-06)

Primary citation

Koh, E.,Kim, U.,Cho, H.S.
Catalytic DxD motif caged in Asx-turn and Met-aromatic interaction attenuates the pathogenic glycosylation of SseK2/NleB2 effectors.
Sci Rep, 12:19288-19288, 2022

PubMed Abstract: Pathogenic bacteria encode virulent glycosyltransferases that conjugate various glycans onto host crucial proteins, which allows adhesion to mammalian cells and modulates host cellular processes for pathogenesis. Escherichia coli NleB1, Citrobacter rodentium NleB, and Salmonella enterica SseK1/3 type III effectors fatally glycosyltransfer N-acetyl glucosamine (GlcNAc) from UDP-GlcNAc to arginine residues of death domain-containing proteins that regulate host inflammation, intra-bacterial proteins, and themselves, whose post-translational modification disrupts host immune functions and prolongs bacterial viability inside host cells. However, unlike the similar NleB1/SseK1/SseK3, E. coli NleB2 and S. enterica SseK2 show deficient GlcNAcylation and neither intra-bacterial glycosylation nor auto-glycosylation. Here, as the major factor in SseK2/NleB2 deficiency, we focused on the catalytic Asp-x-Asp (DxD) motif conserved throughout all O-/N-glycosyltransferases to coordinate Mn. All DxD motifs in apo-glycosyltransferases form Type-I-turns for binding Mn, similar to the ligand-bound DxD motif, whereas TcnA/SseK2/NleB2 DxD motifs form Asx-turns, which are unable to bind Mn. Interestingly, methionine of the NleB2 DMD motif forms triple Met-aromatic interactions, as found in age-associated diseases and tumor necrosis factor (TNF) ligand-receptor complexes. The NleB1 A222M mutation induces triple Met-aromatic interactions to steeply attenuate glycosylation activity to 3% of that in the wild type. Thus, the characteristic conformation of the DxD motif is essential for binding Mn, donors, and glycosylate targets. This explains why SseK2/NleB2 effectors with the DxD motif caged in the Asp-/Asn-turn (Asx-turn) and triple Met-aromatic interactions have lower glycosyltransferase activity than that of other fatal NleB1/SseK1/SseK3 toxins.

PubMed: 36369343
DOI: 10.1038/s41598-022-22803-y

Experimental method

X-RAY DIFFRACTION (3.45 Å)